ArticleCellular & molecular biology letters2019
Costunolide reduces glycolysis-associated activation of hepatic stellate cells via inhibition of hexokinase-2.
Article in Cellular & molecular biology letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Hexokinase-3 upregulation and histone H3K18 lactylation mediate murine liver fibrosis induced by Echinococcus multilocularis.PLoS neglected tropical diseases · 2026Article
- Glycolysis to lactylation: Unraveling the metabolic and epigenetic landscape in tissue fibrosis (Review).Molecular medicine reports · 2025Review
- Lactate and lactylation in liver diseases: energy metabolism, inflammatory immunity and tumor microenvironment.Frontiers in immunology · 2025Review
- Role of lactate and lactate metabolism in liver diseases (Review).International journal of molecular medicine · 2024Review
- Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective.Metabolites · 2024Review
- Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis.Frontiers in immunology · 2024Review
- Fibrosis Development Linked to Alterations in Glucose and Energy Metabolism and Prooxidant-Antioxidant Balance in Experimental Models of Liver Injury.Antioxidants (Basel, Switzerland) · 2023Article
- Costunolide alleviated DDC induced ductular reaction and inflammatory response in murine model of cholestatic liver disease.Journal of traditional and complementary medicine · 2023Article
- Natural products target glycolysis in liver disease.Frontiers in pharmacology · 2023Review
- Phytochemicals as Regulators of Tumor Glycolysis and Hypoxia Signaling Pathways: Evidence from In Vitro Studies.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Sodium butyrate inhibits aerobic glycolysis of hepatocellular carcinoma cells via the c-myc/hexokinase 2 pathway.Journal of cellular and molecular medicine · 2022Article
- Correlation of Glucose Metabolism with Cancer and Intervention with Traditional Chinese Medicine.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- A new strategy for osteoarthritis therapy: Inhibition of glycolysis.Frontiers in pharmacology · 2022Review
- Review
- Silencing of CD147 inhibits hepatic stellate cells activation related to suppressing aerobic glycolysis via hedgehog signaling.Cytotechnology · 2021Article
- The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment.Frontiers in oncology · 2021Review
- Glycolysis Rate-Limiting Enzymes: Novel Potential Regulators of Rheumatoid Arthritis Pathogenesis.Frontiers in immunology · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatic stellate cell (HSC) activation is a central event during hepatic fibrosis. Aerobic glycolysis is one of its metabolic hallmarks. Blocking glycolysis is a novel therapeutic option for liver fibrosis. This study investigated the effects of costunolide, a natural product demonstrated to have hepatoprotective effects, on HSC activation and glycolysis.
methodsPrimary HSCs were isolated from rats and cultured through 5 to 6 passages. Cell viability, activation markers, and glycolytic metabolism were examined in primary HSCs using various cellular and molecular approaches.
resultsAt 30 μM, costunolide reduced the viability of HSCs and inhibited the expression of α-smooth muscle actin and collagen I, two key markers of HSC activation. It also decreased glucose uptake and consumption, and reduced the intracellular levels of lactate in HSCs. At 10 mM, the glycolysis inhibitor 2-DG had a similar impact to costunolide at 30 μM: it significantly downregulated the expression of HSC activation markers. The combination of the two compounds produced more remarkable effects. Furthermore, costunolide repressed the expression and activity of hexokinase 2 (HK2), a pivotal rate-limiting enzyme that regulates glycolysis. However, overexpression of HK2 via plasmid transfection significantly reversed the costunolide-mediated downregulation of activation markers in HSCs, indicating that suppression of HK2 was required for costunolide to inhibit glycolysis-associated HSC activation.
conclusionsOur results show that costunolide can suppress HSC activation, and this is associated with inhibition of HK2, which blocks aerobic glycolysis. This suggests that costunolide is an antifibrotic candidate with potential for further development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.